Alpha, alpha-diphenyl-gamma-(1-methyl-2-piperidyl)-butyronitrile



Patented Aug. 18, 1953 2,649,455

UNITED STATES PATENT OFFICE.

a,aDIPHENYL-'y- (1-METHYL-2-PIPERIDYL) BUTYRONITRILE Lewis A. Walter, Madison, Richard H. Barry, Bloomfield, and John R. Clark, Nutley, N. J., assignors to Maltbie Laboratories, Inc., Newark, N. J a. corporation of New Jersey No Drawing. Application March 22, 1951, Serial No. 217,056

1 Claim. I (Cl. 260-293) This invention relates to a new and useful comenough for subsequent; hydrogenation, but was position of matter, a,a-diphenyl- -(l-methyl-2- crystallized from ethanol-when necessary. This piperidyl)-butyronitrile having the formula: reaction may be expressed-as follows:

E 5 HKIJ/ 1320\ OH OH 0 CN H l| l om-cm-o-oN N/ 2' 2' (C 92804 CH9 10 which is valuable as a pharmaceutical particularly as an antispasmodic of the atropine type. It is also useful as an intermediate in the prepara- I tion of other compounds which are useful as phar- N CH2'OHTCCN maceuticals as antispasmodics, by conversion of the nitrile group (CN) to amide, carboxyl, al- CH3 SOPCHK koxyl, urethane, keto, and amino methyl groups. The compound of the present invention may also be used in the formation of quaternary salts such The above salt in 1600 ml. of methanol was hyas the metho-bromide, etho-sulfate, and others drogenated with hydrogen at 100 atmospheres as will occur to those skilled in the art, by changpressure using 15 g. of Raney nickel catalyst at ing the nitrogen atom of the ring to a valence a temperature preferably'below 85 C. The eatof five. alyst and solventwasiremoved .in the usual man- Two methods of preparation of the compound ner and the resultingsyrup'was dissolved in waof the present invention are set forth in the folterand made quite strongly alkaline with sodium lowing examples: hydroxide. 'I'heoil'whichrseparated was the de- Example I sired. product. It. was best purified as the perchlorate salt M. B. 162-16.? C. from methanol. The hydrochloride'was hygroscopic, but the hydrobromide crystallized with one molecule of isopropyl aoetate' o-f crystallization, M. P. '76-'78" C. Av crystalline .tartrate Wasalso obtained. The reactiomoccurring was-as follows;

Ten grams of sodium was dissolved in three liters of dry isopropanol and 386 g. of diphenyl acetonitrile and 210 g. of 2-Viny1pyridine was added. The mixture was refluxed for five hours, then diluted with an equal volume of warm water. On chilling a,a-diphenyl-'y-2(pyridyl) butyronitrile crystallized out and was filtered oil and recrystallized from methanol to give the pure nitrile, M. P. 120-122 C. The reaction taking place may be 40 I N t 1 t expressed as follows. N OHTCHTO CN H2 1 ca a y C SO4CHi OH=OH1 HC-CN H:

CHz-CHz-O-CN C Hag (EH2 H2 0-H CHrCHz-O-ON Three hundred grams of this nitrile was disens solona solved in three liters of dry benzene and gently refluxed with 135 g. of methyl sulfate for twentyfour hours. An almost quantitative yield of methylsulfate salt precipitated and was filtered l o off. It melted at 163-165 C. and was usually pure [3- (N-methyl-Z-piperidyl) ethanol was reacted with thionyl chloride in the usual manner to give the chloride hydrochloride, M. P. 134-137" C. according to the equation:

CHl-OHzOH Bo C12 CHa l A cold solution of fifty grams of this salt in water was treated with an excess of cold sodium hydroxide solution and the free base was extracted with toluene. This toluene solution was dried over potassium carbonate, filtered, and added to a suspension of 54 g. of sodio-diphenyl acetonitrile (prepared from sodamide in the usual manner in toluene). The mixture was stirred and heated at 100 C. for three hours, then cooled, washed with water, and the toluene layer was separated and the solvent removed. The residue of crude a,a-diphenyl-'y-(l-methyl-Z-piperidyl) butyronitrile was purified as the perchlorate salt.

H: H2O $1312 5 H2C\ /C H 4 V N CHa-GHaCl NaOH CH3 H01 Hz C HM) (311;

H2O C-H I? CHz-CHzCl CH3 and H: H2O (EH2 H2C\ /C H N CHa'CH2C1+Na-C-CN CH2 NaCl l I 1? CH2-CH2-C-CN What is claimed is:

LEWIS A. WALTER. RICHARD H. BARRY.

JOHN R. CLARK.

References Cited in the file of this patent UNITED STATES PATENTS Name Date Bockmuhl et a1. Feb. 4, 1941 Number 

